Investigation of the pharmacological properties and biodisposition of the optical isomers (enantiomorphs) of ketamine in laboratory animals will be carried out. Ketamine isomers will be resolved, absolute configuration determined and methods will be developed for their assay in biological tissues. CNS actions will be determined in laboratory animals including the mouse, rat, cat and dog with special emphasis on the intensity of hypnotic, analgesic, post-hypnotic excitatory and toxic effects of the two enantiomorphs. Possible differences between isomers in terms of their effects on operant behavior, convulsive threshold and cardiorespiratory function will also be examined. Attempts will be made to correlate pharmacologic actions with data on biodisposition of the isomers of ketamine to determine if such effects relate to disposition features including formation of active metabolites. Such metabolites will be isolated, identified and synthesized for study of their individual properties. The major objective of the proposal is to establish if an individual isomer offers potential advantages over the other, or over the racemic mixture, in terms of balance between desirable and unwanted effects.